Development and validation of a liquid chromatography tandem mass spectrometry assay for the measurement of faecal metronidazole

Quantification of metronidazole in healthy subjects' feces using an LC–MS/MS method

“…It is acquired from the environment or through the oral–fecal route, which can lead to infection and is the most frequent cause of antimicrobial‐associated diarrhea. Metronidazole (MTZ), an effective, first‐line antibiotic drug, is commonly used to treat anaerobic bacterial infections owing to C. difficile (Asempa & Nicolau, ; D'Ostroph & So, ; Jeffery, Vincent, Ayling, & Lewis, ). Among other antibiotic agents, MTZ is the preferred choice mainly because of its efficacy against vancomycin‐resistant enterococcus and affordable cost (D'Ostroph & So, ).…”

“…It is metabolized in the liver to give five metabolites, including the active hydroxyl metabolite, which has an activity of ~30–65% and a longer half‐life than MTZ. The drug is eliminated from the body through urine and also in feces (mainly in patients) with a half‐life of 6–10 h (D'Ostroph & So, ; Jeffery et al, ). However, in healthy subjects the concentration of MTZ found in feces is negligible owing to efficient enterohepatic recirculation (Krook, Lindström, Kjellander, Järnerot, & Bodin, ).…”

“…Nevertheless, the median response time for the treatment of C. difficile ‐associated disease is 4–5days. As far as the literature is concerned currently there is limited information on methods to determine MTZ in feces compared with plasma and also the relationship between fecal MTZ concentration and response time to treatment (Jeffery et al, ).…”

“…Numerous methods are available in literature to determine MTZ alone (Bolton & Culshaw, ; Cox, Allender, & Yarbrough, ; de Freitas Silva et al, ; Emami, Ghassami, & Hamishehkar, ; Galmier et al, ; Ilomuanya et al, ; Jeffery et al, ; Krook et al, ; Kubodera, Tokumura, & Machida, ; Mustapha, Odunola, Garba, & Obodozie, ; Silva et al, ; Vanol, Sanyal, Shah, & Shrivastav, ; Wibawa, Shaw, & Barrett, ), together with its hydroxy metabolite (Klimowicz, Bielecka‐Grzela, & Tomaszewska, ) and with other drugs like ranitidine (Nascimento, Oliveira, & Macêdo, ) and spiramycin I (Sagan et al, ) in a variety of biological matrices. Analytical techniques such as liquid chromatography with UV (Bolton & Culshaw, ; Cox et al, ; Emami et al, ; Galmier et al, ; Klimowicz et al, ; Krook et al, ; Kubodera et al, ; Mustapha et al, ; Wibawa et al, ), photodiode array (Nascimento et al, ) or mass spectrometry (de Freitas Silva et al, ; Ilomuanya et al, ; Jeffery et al, ; Sagan et al, ; Silva et al, ; Vanol et al, ) detection have been used for the quantification of MTZ in these matrices. The salient features of these methods are assessed in our previous report (Vanol et al, ).…”

“…The salient features of these methods are assessed in our previous report (Vanol et al, ). However, there are very few methods which deal with the analysis of fecal MTZ (Bolton & Culshaw, ; Jeffery et al, ; Krook et al, ). Two of these reports describe measurement of fecal MTZ in patients having Crohn's disease and colitis using HPLC‐UV method (Bolton & Culshaw, ; Krook et al, ).…”